title: Pharmacokinetics of single-dose intragastric and intravenous pregabalin administration in clinically normal horses.
abstract: OBJECTIVE
  To assess pharmacokinetics of pregabalin in horses after a single intragastric or IV dose.
  
  
  METHODS
  5 healthy adult mares.
  
  
  METHODS
  Horses received 1 dose of pregabalin (approx 4 mg/kg) via nasogastric tube in a crossover-design study; after a 3-week washout period, the same dose was administered IV. Food was not withheld. Plasma pregabalin concentrations in samples obtained 0 to 36 hours after administration were measured by use of ultra-performance liquid chromatography with triple quadrupole tandem mass spectrometry. Pharmacokinetic variables were estimated by means of noncompartmental analysis.
  
  
  RESULTS
  Mild sedation was observed in 2 horses following intragastric and IV pregabalin administration. Signs of mild, transient colic or behavioral abnormalities were observed in all horses following IV administration. After intragastric administration, median (range) maximal plasma concentration was 5.0 μg/mL (4.4 to 6.7 μg/mL), time to maximal plasma concentration was 1. 0 hour (0.5 to 2.0 hours), elimination half-life was 8.0 hours (6.2 to 9.4 hours), and area under the curve from time 0 to infinity (AUC0-∞) was 47.2 μg·h/mL (36.4 to 58.4 μg·h/mL). After IV administration, initial concentration was 22.2 μg/mL (19.8 to 27.7 μg/mL), elimination half-life was 7.74 hours (6.94 to 8.17 hours), and AUC0-∞ was 48.3 μg·h/mL (44.8 to 57.2 μg·h/mL). Bioavailability was 97.7% (80.7% to 109.8%). Median predicted values for minimal, mean, and maximal steady-state plasma concentrations after intragastric administration assuming an 8-hour dosing interval were 3.9, 5.3, and 6.3 μg/mL, respectively.
  
  
  CONCLUSIONS
  At a simulated intragastric dosage of approximately 4 mg/kg every 8 hours, median pregabalin steady-state plasma concentration in healthy horses was within the therapeutic range reported for humans. Therapeutic concentrations and safety of this dosage have not been established in horses.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. krm4@cornell.edu
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Mullen
authors.forename: Wayne
authors.initials: W
authors.lastname: Schwark
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Divers
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D004333:Drug Administration Routes; D006207:Half-Life; D006736:Horses / Q000097:blood*; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000700:Analgesics; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid